Magnetic resonance imaging (MRI) plays a critically important role in molecular imaging and clinical diagnosis because it is non-invasive and capable of producing images with high spatial and temporal resolution (Laurent, S. et al., Chem. Rev. 108, 2064-2110 (2008); Tassa, C. et al., Acc. Chem. Res. 44, 842-852 (2011); Corot, C. et al., Adv. Drug Deliv. Rev. 58, 1471-1504 (2006)). Approximately 35% of clinical MR scans need contrast agents to improve the sensitivity and diagnostic accuracy (Major, J. L. et al., Acc. Chem. Res. 42, 893-903 (2009)). For example, superparamagnetic iron oxide (SPIO) nanoparticles are the most common T2 contrast agents, such as Feridex™ and Resovist™, especially for the imaging and detection of lesions from normal tissues (Weissleder, R. et al., Radiology 175, 489-493 (1990); Bulte, J. W. M. et al., NMR Biomed. 17, 484-499 (2004); Harisinghani, M. G. et al., N. Engl. J. Med. 348, 2491-2495 (2003); Gao, J. H. et al., Acc. Chem. Res. 42, 1097-1107 (2009)).
However, there are several deficiencies in the presently available T2 contrast agents (e.g., Feridex™ and Resovist™) in clinical use. As they are intrinsically negative contrast agents, false positive diagnosis may be found in the hypointense areas such as blood pooling, calcification, and metal deposition (Terreno, E. et al., Chem. Rev. 110, 3019-3042 (2010); Kim, B. H. et al., J. Am. Chem. Soc. 133, 12624-12631 (2011); Lee, N. et al., Chem. Soc. Rev. 41, 2575-2589 (2012)). In particular, the commercially available T2 contrast agents exhibit poor crystallinity and relatively low relaxivity (Lee, N. et al., Proc. Natl. Acad. Sci. USA. 108, 2662-2667 (2011)). Thus, a limitation of MRI at present is the relatively low sensitivity of the contrast agents (Ananta, J. S. et al., Nat Nanotechnol. 5, 815-821 (2010); Ghosh, D. et al., Nat Nanotechnol. 7, 677-682 (2012). Therefore, there exists an unmet need for new T2 contrast agents with high relaxivity for enabling high-performance MRI.